The present invention is generally in the area of methods for formulation of medical devices, in particular using computer aided design in combination with solid free-form fabrication technology.
Many drug regimes require hospitalization or repeated visits because they must be carefully dosed for individual patients or are too complicated for patients to administer themselves. Significant cost savings could be realized if hospital stay and visits were reduced by use of drug delivery devices that accurately deliver drugs at predefined rates for individual patients. Many other drugs which are self-administered have low efficacy because patient compliance is low, even when drugs are supposed to be taken on a simple dosage regime such as once a day.
A number of approaches have been proposed as a means for controlled drug delivery which avoids some of the problems with patient compliance. In most of these cases, this has been achieved by encapsulation of the drug in a polymeric material which releases drug by diffusion, degradation, or a combination of diffusion and degradation, over time. Methods include solvent casting, solvent evaporation, solvent extraction, spray drying, and compression molding. The resulting devices are in the form of tablets, slabs, microparticles, microspheres, and microcapsules. Multiphase release is achieved by encapsulating drug within multiple layers having different release profiles.
One of the problems with the current technology for drug manufacture is the lack of precision and resulting lack of quality control. This in turn causes a lack of precision in the release rates of the encapsulated drug. It also limits the types of multiphasic release to one or two "bursts".
Construction of drug delivery devices which could release drugs according to complex prescribed temporal patterns would increase patient compliance by reducing the number of times a patient must administer the drug. No such methods have been reported at this time, however.
Similarly, a number of approaches have been proposed for construction of synthetic polymeric matrices for growth of cells in vivo, for example, to replace organ function or to provide structural support, i.e., new bone. Such methods have been reported by Vacanti, et al., Arch. Surg. 123, 545-549 (1988), U.S. Pat. No. 4,060,081 to Yannas, et al., U.S. Pat. No. 4,485,097 to Bell, and U.S. Pat. No. 4,520,821 to Schmidt, et al. In general, however, the methods used by Vacanti, et al., and Schmidt, et al., involved selecting and adapting existing compositions for implantation and seeding with cells, while the methods of Yannas and Bell were used to produce very specific structures.
Tissue regeneration devices must be porous with interconnected pores to allow cell and tissue penetration; however, factors such as pore size, shape and tortuosity can all affect tissue ingrowth but are difficult to control using standard processing techniques. None of the prior art methods, however, can be used to construct specific structures from biocompatible synthetic polymers, having defined pore sizes, particularly different pore sizes within the same structure, especially in discrete regions of the structure.
It is therefore an object of the present invention to provide methods and compositions made according to complex temporal patterns for use in drug delivery and tissue regeneration.
It is an object of the present invention to provide methods and compositions for making complex medical devices of erodible or erodible and non-erodible materials which can be used as drug delivery devices or for seeding of cells.
It is a further object of the present invention to provide methods that operate with high precision and reproducibility to produce medical devices.
It is a still further object of the present invention to provide bioerodible devices which are structurally stable during erosion.